The aim of this proposal is to examine the role of NAD and ADP-ribosylation of chronosomal proteins in the regulation of myocardial hypertrophy and hyperplasia. We postulate that changes in NAD secondary to alterations in myocardial oxygen and energy utilization result in changes in ADP-ribosylation of histone and nonhistone nucleoproteins and/or RNA and DNA polymerases. RNA and DNA synthesis is regulated by differences in the accessibility of the DNA template or alteration in the polymerase enzyme activity. In this study we will determine whether changes in NAD and poly (ADP-ribose) levels are related to changes in RNA and DNA synthesis. Three models of myocardial cell growth in rats will be studied: pressure overload myocardial hypertrophy, hypoxia induced hyperplasia in neonatal hearts, and hyperplasia in neonatal hearts, and hypoxia in adult hearts. The possible remuscle and nonmuscle cells will be isolated and studied separately. We will measure NAD, ADP-ribose, and poly (ADP-ribose) levels in cardiac muscle and nonmuscle cells in various states of cell growth. Changes in the rate of synthesis of poly (ADP-ribose) from labelled NAD as well as its degradation by poly (ADP-ribose) glycohydrolase will be determined. Finally we will examine the effect of altering the level of poly (ADP-ribose) with exogenous agents on DNA and RNA synthesis. These studies will provide a basis for further investigation of the role of poly (ADP-ribose) in the regulation of nucleic acid synthesis in the myocardium.